CN101584693A - Pralidoxime chloride-containing drug composition and method for preparing same - Google Patents
Pralidoxime chloride-containing drug composition and method for preparing same Download PDFInfo
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- CN101584693A CN101584693A CNA2008101122458A CN200810112245A CN101584693A CN 101584693 A CN101584693 A CN 101584693A CN A2008101122458 A CNA2008101122458 A CN A2008101122458A CN 200810112245 A CN200810112245 A CN 200810112245A CN 101584693 A CN101584693 A CN 101584693A
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Abstract
The invention relates to the technical field of medicaments, in particular to a pralidoxime chloride-containing medicinal composition and a method for preparing the same. The medicinal composition solves the problems of poor stability, short expiry date and the like existing in similar medicaments sold in the present markets, and has the characteristics of high stability, small drug-using volume, and convenient storage and transportation.
Description
Technical field
The present invention relates to medical technical field, the definite a kind of pharmaceutical composition that contains pralidoxime chloride and preparation method thereof of saying so.
Background technology
Organic phosphorus compound comprises organophosphorus toxicants and organophosphorus pesticide such as parathion, demeton, thimet, Soviet Unionization 203, Mortopl, metrifonate, dichlorvos, Rogor, omethoate, schradane, Malathion etc., organophosphorus pesticide is that China uses the pesticide the widest, that consumption is maximum at present, in production, transportation, keeping and the use of organophosphorus pesticide, careless slightly, just may poison.
It is one of common emergency case of internal medicine that organophosphorus compound is poisoned, the reason of poisoning is to make acetylcholine esterase inactivation in the body, produce excessive acetylcholine, cause nausea, vomit, symptoms such as stomachache, bronchus secretion are many, myosis, decreased heart rate, blood pressure drops, because of respiratory failure due to the pulmonary edema is main causes of death.The organic phosphorus compound poisoning morbidity is swift and violent, just can cause death in several minutes, therefore, must rescue at once.
Cholinesterase reactivator such as pralidoxime (also being referred to as pralidoxime iodide), pyraloxime methylchloride (also being referred to as pralidoxime chloride) and obidoxime chloride etc. are the important antidotes of acute organophosphorus pesticide poisoning.The reactivation agent can make the organophosphate poisoning enzyme recover hydrolysis ability, and pralidoxime chloride is stronger than the detoxification ability of pralidoxime iodide, good water solubility, toxic and side effects are less, but intramuscular injection; But be to use in the market the folk prescription pyraloxime methylchloride injection the sold poisoning symptom due to can not the facedown acetylcholine.
The muscarinic action of acetylcholine in energy such as anticholinergic atropine sulfate and the scopolamine antagonist, lax several kind of smooth muscle cells, suppress multiple glandular secretion, accelerate heart rate and platycoria, thereby effectively alleviate poisoning symptom, but be to use the folk prescription Sal-Tropine on the market can not recover cholinesterase activity.
The antidote of organophosphate poisoning should contain cholinesterase reactivator pralidoxime chloride and anticholinergic atropine sulfate simultaneously, both can recover cholinesterase activity, can alleviate poisoning symptom again, so the antidote for the treatment of both the principal and secondary aspects of a disease.
At present existing a kind of compound recipe pralidoxime chloride injection (aqueous injection), contain pyraloxime methylchloride, atropine sulfate, Benactyzire (benactyzine) and stabilizing agent, can be to the muscarinic action of anti-acetylcholine, acetylcholine esterase to inactivation reactivates effect again, stronger maincenter and periphery cholinolytic effect and acetylcholine esterase re-activation effect are arranged, effect rapidly, the length of holding time, avoided repeatedly frequent medication, but intramuscular injection, but intravenous injection in case of necessity, easy to use, be particularly suitable for doing first dose of antidote, reduce mortality rate thereby the respiratory failure incidence rate is descended, clinical use has obtained better curative effect.But its shortcoming has: 1, the poor stability of this compound medicine in water, and effect duration is short, also has the phenomenon at effect medicine decomposition failure in the phase, is unfavorable for long term store and transportation; 2, liquid drugs injection Chinese medicine concentration is lower, uses volume bigger, need carry out multi-point injection to the patient, causes patient's medication misery; 3, the stabilizer element that is contained belongs to the non-pharmaceutic adjuvant without administrative approval, easily the patient is produced toxic and side effects.
Summary of the invention
The purpose of this invention is to provide a kind of good stability the treatment organophosphate poisoning contain pralidoxime chloride pharmaceutical composition and preparation method thereof.
Another object of the present invention provides the pharmaceutical composition of a kind of concentration height, easy to use, treatment organophosphate poisoning that toxic and side effects is littler.
For achieving the above object, the present invention is by the following technical solutions:
The pharmaceutical composition of described treatment organophosphate poisoning is made up of cholinesterase reactivator pralidoxime chloride and anticholinergic atropine sulfate and hydrochloric acid Benactyzire.
The medicinal forms of the pharmaceutical composition of described treatment organophosphate poisoning is an injectable powder, can be lyophilized injectable powder, can be sterile powder injection.
Pyraloxime methylchloride in the described pharmaceutical composition: atropine sulfate: the ratio of the parts by weight of hydrochloric acid Benactyzire is 30: 1: 1～150: 1: 1.
The preparation of described pharmaceutical composition injectable powder need be added the pH regulator agent, and the preferable range of pH value is 2.5～3.6, the pH regulator agent is organic acid or mineral acid, is selected from citric acid, acetic acid, lactic acid, adipic acid, caproic acid, butene dioic acid, propanoic acid, formic acid, malic acid, carbonic acid, hydrochloric acid, tartaric acid, phosphoric acid, Metaphosphoric acid, sulphuric acid, nitric acid, succinic acid, boric acid, phytic acid, butanoic acid, edetic acid, sorbic acid, salicylic acid, lauric acid, para-amino benzoic acid, ascorbic acid, the benzoic acid one or more.
The preparation of described pharmaceutical composition injectable powder also contains lyophilizing filler (proppant), is selected from mannitol, sodium chloride, lactose, dextran, gelatin, lactose, maltose, polyvinylpyrrolidone, the sorbitol one or more.The ratio of weight and number of medicine and lyophilizing filler is 1: 0～1.
The implementation of the object of the invention is: the preparation method of compound recipe pralidoxime chloride freeze-dried powder comprises the steps:
Take by weighing pralidoxime chloride: atropine sulfate: the ratio of the parts by weight of hydrochloric acid Benactyzire is 30: 1: 1～150: 1: 1, take by weighing frozen-dried supporting agent again, the weight ratio of the weight sum of frozen-dried supporting agent and three kinds of principal agents is 0～1: 1, in principal agent and proppant, add water for injection and make its dissolving, add an amount of pH regulator agent, the control pH value is between 2.0～4.0, the active carbon that adds configuration amount 0.01～0.1% (W/V) again stirs room temperature absorption down 30 minutes, filter carbon removal, benefit adds to the full amount of water for injection, stir, again through the 0.22um filtering with microporous membrane, check, aseptic subpackaged after the assay was approved in the 10ml cillin bottle, the false add plug, after sending the freeze dryer lyophilizing, cover tight plug, roll aluminium lid and get final product.
Freeze drying process is: earlier freeze dryer freeze drying box temperature is reduced to-40 ℃, goods are put into pre-freeze 4 hours, guarantee that goods freeze fully, start vacuum pump, after treating that vacuum reaches requirement, carry out sublimation drying, temperature maintenance between-20 ℃～-40 ℃, and was kept 16 hours, be warming up to 30 ℃ with 5 ℃ programming rate per hour then, be incubated 10 hours, remove residual moisture as far as possible, heat preservation and dryness is 1～2 hour again.
Advantage of the present invention is:
1, freeze-dried powder can effectively be avoided one or more materials unsettled phenomenon in aqueous solution in pralidoxime chloride, hydrochloric acid Benactyzire, the atropine sulfate, than injection stable performance, helps long term store and transportation.
2, drug level can improve, and the injection volume reduces during use, makes the injection site number also reduce, and has alleviated patient's misery, is beneficial to the quick performance of drug effect in the urgent rescue simultaneously.
3, avoid using non-medicinal stabilizer element in the liquid drugs injection, reduced toxic and side effects the patient.
Below in conjunction with embodiment the present invention is described in further details, but the present invention is not subjected to the restriction of these embodiment.
The specific embodiment
Embodiment 1: lyophilized injectable powder
(1) preparation prescription
Pralidoxime chloride 400g
Hydrochloric acid Benactyzire 3g
Atropine sulfate 3g
Saturated citric acid soln is regulated pH2.5～3.6
Water for injection adds to 3000ml
(2) preparation method
Indoor 100 grades of sterile workings, with water for injection pralidoxime chloride 400g, hydrochloric acid Benactyzire, atropine sulfate are made into the 2500ml medicinal liquid, stirring makes dissolving, the needle-use activated carbon that adds 0.05% (W/V) stirs evenly, room temperature absorption 30 minutes, filtering decarbonization, regulate liquid PH value to 3.0 with saturated citric acid soln, stir evenly, add the injection water, shake up to 3000ml.
Get above-mentioned filtrate and use the degerming of 0.22um filtering with microporous membrane, sampling and measuring pH value and content.After the filtrate passed examination in the cillin bottle of packing and 10ml, every bottled 3ml, plug beyond the Great Wall partly, frozen drying, aluminium lid is covered in tamponade again, rolls mouthful promptly.
This process using frozen drying method.Freeze-drier is carried out aseptic process, and freeze dryer freeze drying box temperature is reduced to-40 ℃ then, and goods were put into pre-freeze 4 hours, guarantee that goods freeze fully, start vacuum pump, treat that vacuum reaches requirement after, carry out sublimation drying, temperature maintenance between-20 ℃～-40 ℃, and was kept 16 hours, be warming up to 30 ℃ according to 5 ℃ programming rate per hour then, be incubated 10 hours, remove residual moisture, heat preservation and dryness is 1～2 hour again, tamponade capping then as far as possible.
The pharmaceutical composition good stability of injectable powder is easy to storage and transportation; Do not contain stabilizer element, reduced the generation of side effect; Be cillin bottle or glass bottle, be convenient to remain the preservation of medicinal liquid.
In the preparation process of lyophilized injectable powder, different pH value specifically sees Table 1. to the influence that forms of this product
Effect after the lyophilizing under the different pH value of table 1
Embodiment 2: lyophilized injectable powder
(1) preparation prescription
Pralidoxime chloride 200g
Hydrochloric acid Benactyzire 3g
Atropine sulfate 3g
Saturated citric acid soln is regulated pH2.5～3.6
Water for injection adds to 3000ml
(2) preparation method: with embodiment 1.
Embodiment 3: lyophilized injectable powder
(1) preparation prescription
Pralidoxime chloride 200g
Hydrochloric acid Benactyzire 5g
Atropine sulfate 5g
Saturated citric acid soln is regulated pH2.5～3.6
Water for injection adds to 3000ml
(2) preparation method: with embodiment 1.
Embodiment 4: lyophilized injectable powder
(1) preparation prescription
Pralidoxime chloride 300g
Hydrochloric acid Benactyzire 3g
Atropine sulfate 3g
Mannitol 30g
Saturated citric acid soln is regulated pH2.5～3.6
Water for injection adds to 3000ml
(2) preparation method: with embodiment 1.
Embodiment 5: lyophilized injectable powder
(1) preparation prescription
Pralidoxime chloride 500g
Hydrochloric acid Benactyzire 7g
Atropine sulfate 7g
Lactose 100g
Saturated citric acid soln is regulated pH2.5～3.6
Water for injection adds to 3000ml
(2) preparation method: with embodiment 1.
Experimental example 1: quality examination
Get above-mentioned injectable powder, carry out related substance inspection, safety inspection, endotoxin inspection, uniformity of dosage units inspection, sterility test, the equal conformance with standard of result by the method for Chinese Pharmacopoeia regulation.
Experimental example 2: stability test
One, hot test
1, method:
(1) assay: HPLC method
Instrument: Tianjin, island high performance liquid chromatograph
Chromatographic column: C
185 μ m, 4.6 * 250mm
Item flows: (get 0.2mol/L sodium dihydrogen phosphate 90ml with methanol-acetonitrile-phosphate buffer, add 1mol/L phosphoric acid solution 10ml, regulate pH value to 3.0 with triethylamine and add sodium lauryl sulphate 2.66g, thin up shakes up to 400ml) (200: 4000: 400)
Detect wavelength: 220nm
Algoscopy: the content under the accurate content uniformity item an amount of (being equivalent to pralidoxime chloride 200mg approximately), the accurate title, decide, and puts in the 25ml measuring bottle, is diluted to scale with mobile phase, shakes up.Precision is measured 1ml, puts in the 50ml measuring bottle, is diluted to scale with mobile phase, shakes up, as need testing solution; Precision is measured 10 μ l, injects chromatograph of liquid, the record chromatogram, other the 80 ℃ of drying under reduced pressure of learning from else's experience are an amount of to the pralidoxime chloride reference substance of constant weight, accurate claim fixed, with the mobile phase dissolving and quantitatively dilution make the solution product solution in contrast that contains 160 μ g among every 1ml, measure with method.Press external standard method with calculated by peak area.
(2) Determination of Content Uniformity: HPLC method
Instrument: Tianjin, island high performance liquid chromatograph
Chromatographic column: C
185 μ m, 4.6 * 250mm
Item flows: (get 0.2mol/L sodium dihydrogen phosphate 90ml with methanol-acetonitrile-phosphate buffer, add 1mol/L phosphoric acid solution 10ml, regulate pH value to 3.0 with triethylamine and add sodium lauryl sulphate 2.66g, thin up shakes up to 400ml) (200: 400: 400)
Detect wavelength: 220nm
Algoscopy: precision is measured 10 bottles of this product, whenever adds water 4ml and makes dissolving, puts respectively in the 25ml measuring bottle, is diluted to scale with mobile phase, shakes up, as need testing solution.Precision is measured 10 μ l, injects chromatograph of liquid, the record chromatogram; Other hydrochloric acid Benactyzire reference substance of being dried to constant weight and an amount of of learning from else's experience 105 ℃ through 120 ℃ of atropine sulfate reference substances that are dried to constant weight, accurate claim fixed, with mobile phase dissolving and the quantitative dilution solution product solution in contrast of making sulfur acid atropine 120 μ g and hydrochloric acid Benactyzire 120 μ g among every 1ml.Measure with method.
Calculating every bottle by external standard method respectively with peak area is 100 relative amount with hydrochloric acid Benactyzire and each 3mg of atropine sulfate.
(3) related substance: HPLC method
Instrument: Tianjin, island high performance liquid chromatograph
Chromatographic column: C
185 μ m, 4.6 * 250mm
Item flows: (get 0.2mol/L sodium dihydrogen phosphate 90ml with methanol-acetonitrile-phosphate buffer, add 1mol/L phosphoric acid solution 10ml, regulate pH value to 3.0 with triethylamine and add sodium lauryl sulphate 2.66g, thin up shakes up to 400ml) (200: 4000: 400)
Detect wavelength: 220nm
The algoscopy precision is measured this product 0.22g (being equivalent to pralidoxime chloride 200mg approximately), puts in the 25ml measuring bottle, is diluted to scale with mobile phase, shakes up.Precision is measured 1ml, puts in the 50ml measuring bottle, is diluted to scale with mobile phase, shakes up, as need testing solution; Precision is measured need testing solution 1ml, puts in the 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, in contrast solution.According to the method under the assay item, precision is measured contrast solution 10 μ l, inject chromatograph of liquid, regulate detection sensitivity, make the main peak height be about 20% of monitor full scale, get each 10 μ l of above-mentioned two kinds of solution again, inject chromatograph of liquid respectively, the record chromatogram, the record chromatogram is to 7 times of test sample main peak retention time.Each impurity peak area sum must not be greater than the main peak area (1.0%) of contrast solution in the chromatogram of need testing solution.
2, result: see Table 2～3.
(1) outward appearance: high temperature was placed 10 days for 60 ℃, and the injectable powder outward appearance is without any variation; Injection changes.
(2) content: injectable powder changes not obvious; The injection changes of contents is obvious, and is obviously on a declining curve.
(3) related substance: injectable powder changes not obvious, does not present increase trend; Injection changes obviously, shows a rising trend.
3, conclusion: the Heat stability is good of injectable powder.
Table 2 freeze-dried powder hot test result
Annotate: wherein " content " is the labelled amount of pralidoxime chloride, hydrochloric acid Benactyzire, atropine sulfate wherein; " uniformity of dosage units " is the sign content of hydrochloric acid Benactyzire, atropine sulfate; " related substance " is the content of the impurity that determines with self-controlled method.
Table 3 injection hot test result
Two, light durability test:
1, method:
Instrument: (adjusting illumination is 4500lx ± 500lx) to YB-2 type clarity detector
(1) assay: HLPC method (with the thimble test operation)
(2) uniformity of dosage units: HLPC method (with the thimble test operation)
(3) related substance: HLPC method (with the thimble test operation)
2, result: see Table 4～5.
(1) outward appearance: illuminance 4500lx ± 500lx placed 10 days, and the injectable powder outward appearance is without any variation.Injection changes slightly.
(2) content: injectable powder changes not obvious; The injection changes of contents is obvious, and is obviously on a declining curve.
(3) related substance: injectable powder changes not obvious, does not present increase trend; Injection changes obviously, shows a rising trend.
3, conclusion: the light stability of injectable powder is good.
Table 4 freeze-dried powder exposure experiments to light result
Annotate: wherein " content " is the labelled amount of pralidoxime chloride, hydrochloric acid Benactyzire, atropine sulfate wherein; " uniformity of dosage units " is the sign content of hydrochloric acid Benactyzire, atropine sulfate; " related substance " is the content of the impurity that determines with self-controlled method.
Table 5 injection exposure experiments to light result
Three, accelerated test
1, method:
Condition: 40 ± 2 ℃ of temperature, RH 75 ± 5%
(1) assay: HLPC method (with the thimble test operation)
(2) uniformity of dosage units: HLPC method (with the thimble test operation)
(3) related substance: HLPC method (with the thimble test operation)
2, result: see Table 6～8.
(1) outward appearance: the injectable powder outward appearance is without any variation.
(2) content: change not obvious
(3) related substance: change not obviously, do not present increase trend.
3, conclusion: the effect duration that can calculate out according to the accelerated test result is 2 years, the having good stability of powder pin.
Table 61 batch accelerated test is investigated the result
Table 72 batch accelerated test is investigated the result
Table 83 batch accelerated test is investigated the result
Experimental example 3
The test of injectable powder specific safety
One, external test tube method hemolytic test
Method is got 7 in test tube, respectively adds 2.5ml 2% red cell suspension, and 1～No. 5 pipe adds 0.1～0.5m injectable powder respectively, and No. 6 pipes add 2.5ml 0.9% sodium chloride injection and make negative control, and No. 7 pipes add the 2.5ml distilled water and make positive control.Beginning is observed once every 15min behind 37 ℃ of water bath heat preservations, observes once every 1h behind the 1h, continuous 3h, and the haemolysis situation is respectively managed in perusal, capable in case of necessity microscope inspection.
At once haemolysis occurs after No. 7 positive control pipes add distilled water as a result, the clear and bright redness of solution, the pipe end, do not have the erythrocyte deposition in the pipe; 1～No. 5 test sample pipe continues the 3h observation and does not see haemolysis, the visible obviously layering of liquid in pipe, and supernatant liquid is a colourless transparent liquid, and, there are a large amount of erythrocyte depositions at the pipe end, and jog is respectively managed erythrocyte and is scattered, and contrasts the indifference opposite sex with No. 6 negative control pipes and changes.
Under this experimental condition of conclusion, injectable powder does not have obvious external haemolysis and cohesion to tame rabbit erythrocyte.
Two, whole body active hypersensitive test (ASA)
Method is got 18 of Healthy female Cavia porcelluss, is divided into 3 groups of test sample group, negative control group and positive controls at random by body weight.Difference ip corresponding solution, totally 3 sensitization next day that each organizing Cavia porcellus.10d respectively organizes Cavia porcellus and excites with 2 times of sensitizing doses foot sole of the foot iv administration after the last sensitization.
The result excites back 30min to observe as seen continuously: occur grabbing obviously anaphylaxiss such as nose, perpendicular hair, sneeze, dyspnea, spasm, shock after the positive controls Cavia porcellus excites at once, 6 Cavia porcelluss are all dead in exciting back 5min, be judged as " 20 " by whole body sensitization evaluation criterion, belong to the extremely strong positive.Generally in order, do not have obvious anaphylaxis after test sample group Cavia porcellus excites, do not see significant change with the negative control group Cavia porcellus, be judged as " 0 " by whole body sensitization evaluation criterion, anaphylaxis is negative.Duration of test Cavia porcellus body weight gain is good, does not see tangible ANOMALOUS VARIATIONS.
Under this experimental condition of conclusion, injectable powder does not have obvious sensitization to Cavia porcellus.
Three, vascular stimulation test
Method is got 4 of healthy rabbits, every rabbit right edge intravenous drip injectable powder clinical application concentration solution of picking up the ears, left side auricular vein instillation equal-volume 0.9% sodium chloride injection.Administration volume 1ml/, the about 0.5～1.0ml/min of injection speed.Every day 1 time, continuous 5 days.And behind last administration 48h, injection site proximal part clip ear edge, 4% neutral formalin solution is fixed, the conventional organization section, observation has or not thrombosis, endothelial injury and other pathological changes.
Duration of test as a result, rabbit does not see irritations such as obvious hyperemia, redness generally in order.Microscope inspection skin, epidermis and subcutaneous tissue and cartilage structure are clear.Blood vessel endothelium is complete, and no thrombosis forms, and compares no significant difference with control sides.
Under this experimental condition of conclusion, injectable powder does not have the obvious stimulation effect to the rabbit auricular vein.
Four, muscle irritation test
Method is got 4 of healthy rabbits, consubstantiality left and right sides self matching type.Earlier, expose left and right sides quadriceps femoris with the electric hair cutter cropping, then with aseptic manipulation on every rabbit left side (L), right (R) both sides depilation place injects 0.9% sodium chloride injection and injectable powder medicinal liquid respectively.Administration volume 1.0ml/ side, 5 administrations.And behind last administration 48h, dissect and take out quadriceps femoris, vertically cut the irritant reaction situation of perusal injection site muscular tissue.4% neutral formalin solution is fixed, the conventional organization section, and observation has or not thrombosis, endothelial injury and other pathological changes.
Duration of test as a result, rabbit does not see irritations such as obvious hyperemia, redness generally in order.The microscope inspection muscle fiber is organized clear, the structural integrity of band, and no degeneration, necrosis and inflammatory reaction are not seen obvious pathological change with control sides.
Under this experimental condition of conclusion, injectable powder does not have the obvious stimulation effect to tame rabbit muscle.
Claims (7)
1, a kind of pharmaceutical composition for the treatment of organophosphate poisoning contains active component pralidoxime chloride, atropine sulfate and hydrochloric acid Benactyzire.
2, pharmaceutical composition according to claim 1 is characterized in that, described pralidoxime chloride: atropine sulfate: the parts by weight of hydrochloric acid Benactyzire are 30: 1: 1～150: 1: 1.
3, pharmaceutical composition according to claim 1 and 2, it is characterized in that, its dosage form is a lyophilized injectable powder, its prescription is formed the weight fraction comprise pralidoxime chloride, atropine sulfate, hydrochloric acid Benactyzire, lyophilized powder proppant and each component of PH regulator than being 1 part of pralidoxime chloride, atropine sulfate, hydrochloric acid Benactyzire, 0～1 part of frozen-dried supporting agent, the PH regulator is an amount of, and every bottle of lyophilized injectable powder contains pralidoxime chloride 1～1000mg, atropine sulfate 1～10mg, hydrochloric acid Benactyzire 1～10mg.Preferred pralidoxime chloride 1～500mg, atropine sulfate 1～5mg, hydrochloric acid Benactyzire 1～5mg.
4, according to the described arbitrary preparation of drug combination method of claim 1 to 3, it is characterized in that, get in the lyophilized powder proppant and pralidoxime chloride, hydrochloric acid Benactyzire, atropine sulfate dissolving and water for injection of recipe quantity, be adjusted to suitable scope with the PH regulator, the active carbon room temperature that adds configuration amount 0.01～0.1% (W/V) stirred 20～50 minutes, filtering decarbonization is with the filtering with microporous membrane degerming of 0.22um, fill.Lyophilization, gland.
5, pharmaceutical composition according to claim 1 and 2, it is characterized in that, described PH regulator is organic acid or mineral acid, is selected from citric acid, acetic acid, lactic acid, adipic acid, caproic acid, butene dioic acid, propanoic acid, formic acid, malic acid, carbonic acid, hydrochloric acid, tartaric acid, phosphoric acid, Metaphosphoric acid, sulphuric acid, nitric acid, succinic acid, boric acid, phytic acid, butanoic acid, edetic acid, sorbic acid, salicylic acid, lauric acid, para-amino benzoic acid, ascorbic acid, the benzoic acid one or more.
6, pharmaceutical composition according to claim 1 and 2, it is characterized in that, described lyophilized injectable powder also contains the lyophilizing filler, is selected from mannitol, sodium chloride, lactose, dextran, gelatin, lactose, maltose, polyvinylpyrrolidone, the sorbitol one or more.The ratio of weight and number of medicine and lyophilizing filler is 1: 0～1.
7, according to right 1 to 6 described arbitrary pharmaceutical composition, it is characterized in that: the pH proper range selects 2～4, preferred 2.5～3.6.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102727433A (en) * | 2012-07-13 | 2012-10-17 | 成都力思特制药股份有限公司 | Preparation method of pralidoxime chloride injection |
| CN107530285A (en) * | 2015-04-29 | 2018-01-02 | 加利福尼亚大学董事会 | Detoxified using nano-particle |
-
2008
- 2008-05-22 CN CNA2008101122458A patent/CN101584693A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102727433A (en) * | 2012-07-13 | 2012-10-17 | 成都力思特制药股份有限公司 | Preparation method of pralidoxime chloride injection |
| CN107530285A (en) * | 2015-04-29 | 2018-01-02 | 加利福尼亚大学董事会 | Detoxified using nano-particle |
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